Microwave Ablation Lowers Cortisol in Man, 71, With Ectopic Cushing’s

Procedure uses electromagnetic energy to destroy tissue with no surgery

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by Andrea Lobo |

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A 71-year-old man diagnosed with ectopic Cushing’s syndrome was cured of the rare disorder after having both adrenal glands subjected to microwave ablation — a minimally-invasive procedure that uses electromagnetic energy to generate heat and destroy a small portion of tissue.

The procedure immediately worked to lower the man’s elevated cortisol levels, which had continued despite the patient twice undergoing pituitary surgery and being treated with medications. Given several comorbidities, or coexisting disorders, the man was not a candidate for invasive adrenal gland surgery to treat his high cortisol levels — a condition known as hypercortisolism.

“Bilateral adrenal gland MWA [microwave ablation] effectively cured hypercortisolism in our patient with ectopic [Cushing’s syndrome],” the researchers wrote, adding that this procedure can be an effective option “when surgical resection [removal] and medical therapies are ineffective or contraindicated.”

His case was described in a study titled “Utilization of bilateral percutaneous microwave ablation of the adrenal glands in ectopic Cushing’s syndrome,” published in the journal Radiology Case Reports.

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Cushing’s syndrome comprises a group of disorders characterized by hypercortisolism, or excessive levels of the hormone cortisol in the body. In most cases, it is caused by benign tumors arising in the brain’s pituitary gland — a form of the syndrome called Cushing’s disease. Such tumors elicit excessive production of adrenocorticotropic hormone (ACTH), which will be registered by the adrenal glands sitting atop the kidneys and lead to the overproduction of cortisol.

In rare cases, the cause is an ACTH-producing tumor found outside the pituitary or adrenal glands, which is often difficult to detect. In these cases, patients are said to have ectopic Cushing’s syndrome.

Treatment with microwave ablation

Here, a U.S. medical team reported the case of an older man with ectopic Cushing’s syndrome who was successfully treated for hypercortisolism after undergoing microwave ablation in both adrenal glands.

The man had a history of obesity, type 2 diabetes diagnosed four years earlier, and obstructive sleep apnea identified one year earlier. He originally sought care to have his diabetes managed, and reported significant weight gain, thinning of the skin, and easy bruising — all typical symptoms of Cushing’s.

Brain imaging did not reveal the presence of a tumor in the pituitary gland. Six months later, due to the development of other health issues, he underwent an inferior petrosal sinus sampling that revealed high ACTH levels. This is an invasive procedure in which ACTH levels are measured in blood coming from the veins that drain the pituitary gland, to determine whether there is a tumor in this region that could be causing Cushing’s disease.

The patient was indicated for pituitary surgery, which was performed 11 months after he initially sought treatment. While waiting for surgery, he was treated with ketoconazole, at a dose of 200 mg every eight hours. Ketoconazole, sold as Nizoral, among other brand names, is an anti-fungal medication that can lower cortisol levels. It is approved in Europe to treat Cushing’s, and is used off-label — meaning it is not approved for that indication — in the U.S.

He underwent trans-sphenoidal surgery — the most common procedure to remove pituitary tumors. In this procedure, a surgeon accesses the pituitary gland through the sphenoid sinus, a hollow space in the skull behind nasal passages and below the brain.

Tissue analysis conducted after surgery revealed an enlargement of pituitary tissue that was positive for ACTH. However, after surgery, the man’s cortisol levels remained elevated.

The patient was restarted on ketoconazole, and the surgery was repeated 15 months after the condition was first detected. The second surgery, however, was also ineffective in reducing ACTH or cortisol levels, confirming the diagnosis of ectopic Cushing’s syndrome.

The medical team identified lung and thyroid nodules as possible ACTH sources, but considering the patient had multiple coexisting conditions, surgery to remove these nodules or both adrenal glands was considered too risky.

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Moreover, medical therapies were contraindicated due to interaction with other medications. Yet, treatment of high cortisol was urgent considering the patient’s health condition, the researchers noted.

Treatment-resistant case

A multidisciplinary medical team, together with the patient and his family, made the decision to perform microwave ablation in both adrenal glands. This procedure involves inserting a thin microwave antenna through the skin that is directly placed in the glands. A generator then emits electromagnetic energy in the microwave range that agitates water molecules to produce frictional heat and induce cell death.

Immediately after the procedure, the patient had a decrease in blood cortisol levels. He started taking hydrocortisone and fludrocortisone to manage adrenal insufficiency symptoms. Adrenal insufficiency is a condition in which the adrenal glands fail to produce enough amounts of certain hormones.

Six months after the microwave ablation, cortisol levels were consistent with adrenal insufficiency, and he continued hydrocortisone and fludrocortisone therapy.

At one- and two-year follow-up appointments, the patient had improved clinically regarding weight loss, blood pressure, and blood sugar control. He was, however, still on treatment for adrenal insufficiency.

“Despite our patient’s medical complexities, bilateral adrenal gland [microwave ablation] induced a clinical cure without the increased risks associated with bilateral [surgical removal of the adrenal glands] and complexities of medical management in high-risk patients,” the team wrote.

A literature analysis revealed that bilateral ablation of the adrenal glands was reported in very few cases and applied to patients who failed to respond to conventional therapy. Most patients had a decrease in cortisol levels following the procedure, with subsequent symptom alleviation. However, the time needed to develop adrenal insufficiency varied.

“Larger studies are needed to determine the range of time for patients to develop adrenal insufficiency after bilateral adrenal ablation,” the researchers wrote, of the microwave ablation procedure.

According to the team, these results support that “bilateral adrenal [microwave ablation] should be considered as an effective treatment modality for [Cushing’s syndrome].”